Abstract
During human immunodeficiency virus (HIV) infection, alcohol has been known to induce inflammation while cannabinoids have been shown to have an anti-inflammatory role. For instance cannabinoids have been shown to reduce susceptibility to HIV-1 infection and attenuate HIV replication in macrophages. Recently, we demonstrated that alcohol induces cannabinoid receptors and regulates cytokine production by monocyte-derived dendritic cells (MDDC). However, the ability of alcohol and cannabinoids to alter MDDC function during HIV infection has not been clearly elucidated yet. In order to study the potential impact of alcohol and cannabinoids on differentiated MDDC infected with HIV, monocytes were cultured for 7 days with GM-CSF and IL-4, differentiated MDDC were infected with HIV-1Ba-L and treated with EtOH (0.1 and 0.2%), THC (5 and 10 μM), or JWH-015 (5 and 10 μM) for 4–7 days. HIV infection of MDDC was confirmed by p24 and Long Terminal Repeats (LTR) estimation. MDDC endocytosis assay and cytokine array profiles were measured to investigate the effects of HIV and substances of abuse on MDDC function. Our results show the HIV + EtOH treated MDDC had the highest levels of p24 production and expression when compared with the HIV positive controls and the cannabinoid treated cells. Although both cannabinoids, THC and JWH-015 had lower levels of p24 production and expression, the HIV + JWH-015 treated MDDC had the lowest levels of p24 when compared to the HIV + THC treated cells. In addition, MDDC endocytic function and cytokine production were also differentially altered after alcohol and cannabinoid treatments. Our results show a differential effect of alcohol and cannabinoids, which may provide insights into the divergent inflammatory role of alcohol and cannabinoids to modulate MDDC function in the context of HIV infection.
Highlights
Since the discovery of the Human Immunodeficiency Virus (HIV), the acquired immunodeficiency syndrome (AIDS) epidemic has been consistently associated with substance abuse and in some cases substance abuse treatment has been proposed as AIDS prevention (Metzger et al, 1998; Volkow, 2012)
The monocyte-derived dendritic cells (MDDC) role during human immunodeficiency virus (HIV) infection has been somehow controversial due to the discrepancy regarding HIV infection of MDDC and evidence showing that HIV spreads from virus-containing MDDC to T cells via an infectious synapse (McDonald et al, 2003; Blanchet et al, 2011), MDDC are professional antigen presenting cells and they do get productively infected with HIV as shown by previous reports (Scott-Algara et al, 2008) and our own current findings demonstrating an increase in p24 intracellular levels, p24 secretion, and Long Terminal Repeats (LTR)
Despite MDDC questionable ability to get productively infected with HIV, they play a major role during HIV-1 trans infection of CD4+ T cells as previously reviewed (Agudelo et al, 2010; Rinaldo, 2013)
Summary
Since the discovery of the Human Immunodeficiency Virus (HIV), the acquired immunodeficiency syndrome (AIDS) epidemic has been consistently associated with substance abuse and in some cases substance abuse treatment has been proposed as AIDS prevention (Metzger et al, 1998; Volkow, 2012). Cannabinoids, and HIV Infection comorbidities have been extensively discussed as demonstrated by the review of studies in humans and animal models (Chang et al, 2014; Molina et al, 2015). Substances of abuse have been shown to alter immune functions in vitro and in animal models, there is a lack of studies in humans that correlate immunosuppressive effects with increased incidence of infections, including infection with HIV as previously reviewed (Cabral, 2006; Molina et al, 2010a). As previously reviewed most of the literature has highlighted the independent role of alcohol or marijuana on HIV (Chang et al, 2014; Nair and Agudelo, 2014; Molina et al, 2015; Nair et al, 2015); a side by side comparison of the in vitro effects of alcohol and the role of cannabinoid compounds such as tetrahydrocannabinol (THC) and the synthetic cannabinoid, JWH-015, on HIV infection of monocyte-derived dendritic cells (MDDC) has not been explored
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